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Tremfya

Generic Name: Guselkumab
Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: Immunoglobulin G1, anti-(human interleukin 23) (human CNTO 1959 heavy chain), disulfide with human CNTO 1959λ-chain, dimer
Molecular Formula: C6402H9864N1676O1994S42
CAS Number: 1350289-85-8

Medically reviewed on July 23, 2018

Introduction

Inhibitor of interleukin-23 (IL-23), a proinflammatory cytokine; a recombinant human IgG1λ monoclonal antibody directed against the p19 subunit of IL-23.1 2 3 6

Uses for Tremfya

Plaque Psoriasis

Management of moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy.1 2 3 4 5 6

Tremfya Dosage and Administration

Administration

Administer by sub-Q injection; IV or IM use not recommended by manufacturer.1

Sub-Q Administration

Available as single-use, prefilled syringes.1

Administer by sub-Q injection into the thigh, lower abdomen, or upper arm; do not make abdominal injections within 2 inches of the umbilicus.1 Use thigh (the preferred site) or abdomen for self-administration; may use upper arm if not self-administered.1 Do not make injections into areas where the skin is tender, bruised, red, hard, thick, or scaly.1 Do not inject into psoriatic lesions.1

Allow guselkumab prefilled syringe to sit at room temperature inside the carton for at least 30 minutes prior to injection; do not warm the drug in any other way (e.g., microwave, hot water).1 Do not remove the needle cap while the drug is warming to room temperature.1 Do not shake prefilled syringe.1

Intended for use under the supervision of a clinician, but may be self-administered if clinician determines the patient and/or caregiver is competent to safely administer the drug after appropriate training.1

Dosage

Adults

Plaque Psoriasis
Sub-Q

100 mg at weeks 0 and 4, followed by 100 mg every 8 weeks.1

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.1

Renal Impairment

Manufacturer makes no specific dosage recommendations.1

Geriatric Patients

Dosage adjustment based on age not necessary.1

Cautions for Tremfya

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Infectious Complications.

Possible increased risk of infections.1 Bacterial, fungal, and viral infections, including gastroenteritis, upper respiratory tract infections, tinea infections, and herpes simplex infections, reported.1

Do not use in patients with clinically important active infections.1 Consider risks and benefits before initiating therapy in patients with chronic infection or history of recurrent infection.1

If a serious infection occurs or does not respond to standard therapy, discontinue guselkumab and closely monitor patient until infection resolves.1

Evaluate all patients for active or latent tuberculosis prior to initiation of guselkumab therapy.1 Do not use in patients with active tuberculosis infection; when indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to guselkumab therapy.1 Also consider antimycobacterial therapy prior to initiation of guselkumab in patients with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment for these indications cannot be confirmed.1 Closely monitor for signs and symptoms of active tuberculosis during and after treatment.1

Immunization

Consider administering all age-appropriate vaccines recommended by current immunization guidelines before initiating guselkumab.1

Avoid live vaccines during therapy.1 (See Vaccines under Interactions.)

Immunogenicity

Formation of antiguselkumab antibodies, including neutralizing antibodies, reported; antiguselkumab antibodies were associated with lower trough concentrations of the drug, but generally not associated with loss of efficacy or injection site reactions.1

Specific Populations

Pregnancy

Data regarding use and associated risks in pregnant women not available.1 Potential for fetal exposure since human IgG crosses the placenta.1

Lactation

Not known whether guselkumab distributes into human milk, affects human milk production, or affects breast-fed infants.1

Consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

No apparent differences in safety and efficacy relative to younger adults; however, insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1

Hepatic Impairment

No formal studies to date.1

Renal Impairment

No formal studies to date.1

Common Adverse Effects

Upper respiratory tract infection1 2 3 (e.g., nasopharyngitis,1 2 3 pharyngitis1 ), headache,1 2 3 injection site reactions,1 2 arthralgia,1 2 elevated hepatic enzymes,1 diarrhea,1 gastroenteritis,1 tinea infections,1 herpes simplex infections.1

Interactions for Tremfya

Drugs Metabolized by Hepatic Microsomal Enzymes

Because elevated levels of certain cytokines during chronic inflammation may alter formation of CYP isoenzymes, antagonism of IL-23 activity by guselkumab could normalize formation of CYP enzymes.1 7 8

Substrates of CYP isoenzymes 1A2, 2C9, 2C19, or 3A4: Limited data suggest interaction potential may be low.1

CYP2D6 substrates: Interaction potential not ruled out by available data.1

CYP substrates: Upon initiation of guselkumab, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment of the CYP substrate as needed, especially if substrate has a narrow therapeutic index.1

Vaccines

Avoid live vaccines.1 No data available regarding response to live or inactivated vaccines in patients receiving guselkumab.1

Specific Drugs

Drug

Interaction

Comments

Acetaminophen

No effect on guselkumab clearance1

Caffeine

Possible effect on caffeine metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation1

Limited data suggest no substantial effect on caffeine AUC1

Dextromethorphan

Possible effect on dextromethorphan metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation1

Limited data cannot rule out interaction potential1

Midazolam

Possible effect on midazolam metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation1

Limited data suggest no substantial effect on midazolam AUC1

NSAIAs (aspirin, ibuprofen)

Aspirin, ibuprofen: No effect on guselkumab clearance1

Omeprazole

Possible effect on omeprazole metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation1

Limited data suggest no substantial effect on omeprazole AUC1

Warfarin

Possible effect on warfarin metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation1

Limited data suggest no substantial effect on warfarin AUC1

Consider monitoring therapeutic effect of warfarin and consider warfarin dosage adjustment as needed upon initiation of guselkumab1

Tremfya Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 49% following sub-Q administration.1

Peak serum concentrations achieved by approximately 5.5 days following a single 100-mg sub-Q dose.1

Pharmacokinetics are dose proportional over a sub-Q dose range of 10–300 mg.1 7

Distribution

Extent

Not known whether distributed into human milk.1

Special Populations

Volume of distribution increases with increasing body weight.1

Elimination

Metabolism

Metabolic pathway not characterized.1

Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.1

Half-life

15–18 days.1

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.1

Clearance increases with increasing body weight.1

Age ≥65 years does not substantially alter clearance.1

Stability

Storage

Parenteral

Injection

2–8°C.1 Keep in original carton and protect from light.1 Do not freeze.1

Actions

  • Binds with specificity to the p19 subunit of IL-23, a naturally occurring cytokine that stimulates production of proinflammatory cytokines, including interleukin-17 (IL-17) and interleukin-22 (IL-22).1 2 3 6 7 IL-17 and IL-22 contribute to chronic inflammation in patients with psoriasis.3 6

  • Disrupts IL-23-mediated signaling and inhibits the release of proinflammatory cytokines and chemokines.1 2 3 7

Advice to Patients

  • Provide all patients with a copy of the manufacturer's patient information (medication guide) and instructions for use with each prescription of the drug.1 Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.1

  • Importance of instructing patient and/or caregiver regarding proper storage, dosage, and administration of guselkumab, including the use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.1

  • Possible increased susceptibility to infections.1 Importance of promptly informing clinician if any signs or symptoms of infection (e.g., fever, sweats, or chills; muscle aches; cough, shortness of breath, or blood in the phlegm; weight loss; warm, red, or painful sores on the body; diarrhea or stomach pain; burning upon urination or increased urination) occur.1

  • Importance of reviewing vaccination status with clinician and receiving all appropriate vaccinations prior to initiation of guselkumab.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., active infection) or any history of tuberculosis or other infections.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Guselkumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

100 mg/mL

Tremfya

Janssen Biotech

AHFS DI Essentials™. © Copyright 2018, Selected Revisions July 23, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Janssen Biotech, Inc. Tremfya (guselkumab) injection for subcutaneous use prescribing information. Horsham, PA. 2017 Oct.

2. Blauvelt A, Papp KA, Griffiths CE et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017; 76:(3):405-17.

3. Reich K, Armstrong AW , Foley P et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial . J Am Acad Dermatol. 2017; 76:(3):418-31.

4. Langley RG, Tsai TF, Flavin S et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2017; https://www.ncbi.nlm.nih.gov/pubmed/28635018

5. Gordon LB, Blauvelt A, Foley P et al. Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: A pooled analysis of the Phase 3 VOYAGE 1 and VOYAGE 2 studies. Br J Dermatol. 2017; https://www.ncbi.nlm.nih.gov/pubmed/28940259

6. Nakamura M, Lee K, Jeon C et al. Guselkumab for the treatment of psoriasis: A review of Phase III trials. Dermatol Ther. 2017; :281-92.

7. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761061Orig1s000: Multi-discipline review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761061Orig1s000MultidisciplineR.pdf

8. Janssen Biotech Inc. Stelara (ustekinumab) injection prescribing information. Horsham, PA; 2017 Oct.

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